Manufacture of aldehyde compounds of diamino-acridines and the novel product resulting therefrom



Patented May 22, 1928.

, warren, STAES A 1,670,740 ear orrlca.

GEORGE W. RAIZISS AND BARRETT C. FISHER, 0F PHILADELPHIA, PENNSYLVANIA,

ASSIGNORS TO THE ABBOTT LABORATORIES, OF CHICAGO, ILLINOIS, A. CORPORA- TION OF ILLINOIS.

MANUFACTURE OF ALDEHYDE COMPOUNDS OF DIAMINO-AGRIDINES AND THE NOVEL PRODUCT RESULTING TI-IEREFROM.

No Drawing. Application filed May 25,

The method of production of di-aminoacridine has long been well known, as has also the production therefrom of 3-6-d1amino-alkyl-acridinium salts. Among these salts, 3,6 -diamin0-10-m-ethylacridinium chloride monohydrochloride and 8,6-d1am1no- 10n1ethylacridinium chloride di-hydrochloride are well known under the trade names Acrifiavine and Neutral Acriflavine respectively. v

The object of the present invention IS the production of a series of generically similar aldehyde addition products from di ainino acridinium. compounds, preferably using as starting or initial material what is commonly sold as acriflavine, 3,6-diam1no-1O- methyl acridinium chloride monohydrochlorids or its salts or its alkyl derivatives. The resultant aldehyde derivatives differ from the so-called Schiifs bases, in that water is not splitoff as with Schiffs bases. These new aldehyde derivatives have marked value in therapy, in that we have found that they have superior bactericidal effects on bacilli, such as staphylococcus aureus and bacillus typhosus; the aromatic salicyl aldehyde derivatives, for instance, showing a greater utility in that regard.

The novel product resulting from our process or method of manufacture of our aromatic aldehyde compounds of diaminoacridine, is characterized by the chemical union of the two amino groups in diaminoacridinium compounds with two aldehyde molecules; and these, for example, may be salicyl-aldehyde or anisic-aldehyde, or cinnamic-aldehyde, or hydro-cinnamic aldehyde, or para-hydroxy-benzaldehyde, the position of the aldehyde group in our new compound being the same in each compound, namely an addition to each amino group of the diamino-acridine nucleus. v

The novel aldehyde derivative produced is essentially an aldehydic addition product of diamino acridine or diamino acridinium compounds, and the process of preparing them is illustrated by the following example; and the particular diamino-acridinium compound selected to illustrate the procedure is the 3-6-diamino-10-methylacridinium chloride mono-hydrochloride, or the so called acriflavine.

At least 7.85 grams or the equivalent of 1923. Serial 11%. 641,521.

empirical formula is C;4I-IMN3CLHCLH,O,

and atomic weight is 314, or the equivalent weight of its salts or alkyl derivatives, is

dissolved inabout 1000 c. .c. of water, to

-which isadded in admixturev 6.10 grams (equivalent to two molecules) of salicyl aldehyde previously dissolved in about 200 c. c.

of methyl alcohol and about 200 c. c. of I hydrochloric acid concentrated. v

The mixture -1s vlgorously shaken for about half an hour and then allowed to stand for several hours or until crystallization results. lhe crystals are isolatedby filtration and washed with about-10 per cent hydrochloric acidand then kept in vacuo until completely dry.

Of'course the above proportions shall be changed in accordance with the molecular weights ofother di-amino acridinium compounds that are used, as well as other aldehydes. i

as follows:

The aldehyde group, which may beeX- pressed by O 0. is so changed that the oxygen which, by means of twovalences, has become attached to the carbon, is changed into hydroxyl, OH. The hydroxyl utilizes only one valence of the carbon in attaching itself to it, so that one bond of the carbon is released and attaches itself to the nitrogen of the amino group, while one of the two, hydrogens, previously combined to nitrogen of the amino group, separates therefrom to join the oxygen previously attached to the carbon by the double bond and is changed to hydroxyl, no water being splitotl'. TIence the process-of addition consistsof the removal of one, hydrogen from the amino group and placing the same hydrogen in the aldehyde group to form a hydroxyl group.

amino group.

This effect takes. place with each amino group of the di-amino-acridinium compound that is used.

The chemical reaction which takes place is i- A graphic representation of it is as follows:' /H /OH The salicyl-aldehyde derivative of di amino acridinium chloride 1s a substance which is crystalline in. character, red in color, with a yellowish tinge when dissolved in water, and would be represented by; the tollowiug structural formula:

1 i on l III i l Nrr/Q ll l CL Olin IlCL OH no a WVe clai1n' 1. An addition product in whichtwo aromatic aldehyde molecules are united'to the amino-groupsof 5,6 di-amino-10- allzyl acridinium' compounds.

4. The process of producing an addition product of diamino-acridines with an aromatie aldehyde; which comprises treating an aqueous solution of a 3,6 di-amino-l0- allzyi acridinium compound With at least two equivalent molecular weights of salicyl aldehyde dissolved in a solution of an alcohol and concentrated hydrochloric.acid, removing the resulting crystals, washing them with dilute hydrochloric acid and drying.

The process of producing anaddition product of a diamino-acridine compound; which comprises treating an aqueous solution of a 3,6-diamino--i0-methyl acridinium chloridemono-hydrochloride (known com-' mereially as acriflavine) with at least two equivalent molecular weights of an aromatic aldehyde dissolved in a solution of alcohol and concentrated hydrochloric acid, removing th resultant product, washing 'itwith dilute hydrochloric acid and drying. The process of producing an addition product of a diamino-acridinc compound, which comprises treating an aqueous solution ofa 3,6-dia-mino-lo-niethyl acridinium chloride monohydrochloride (known cominercially a's acriflavine) with at least two equivalent molecular weights of salicyl aldehyde disssolved in a solution of alcohol and concentrated hydrochloric acid, removingthe resultant product, washing with dilute hydrochloric acidand drying.

in testimony whereof, We have hereunto afiiXed our signatures this May A. D. 1923.

o-Eoaen W. 'mrziss. BARRETTC. FISHER. 

